Investigating Benzene and Metabolite Mediated Alterations in Nrf2 Signaling in Murine Fetal Liver Cells

Author(s):  
Enoch Lam

Leukemia is a cancer of the blood, where the body produces an overabundance of immature white blood cells. It is the most common childhood cancer and possibly originates from chemical exposure during fetal development. Understanding the molecular mechanism and causes of childhood leukemia will help the development of therapeutic and preventative strategies to reduce and treat occurrences of this cancer. Benzene is a non-polar aromatic ring that has been confirmed to cause leukemia in adults. Benzene metabolites can generate free radicals that could potentially be involved in the development of childhood leukemia through in utero exposures. It is found in tobacco smoke, gasoline, industrial solvents and many other substances. Pregnant mothers can be chronically exposed to these substances through daily activities. In order to help determine the mechanism of benzene toxicity, a study was performed to determine the presence of free radicals in the livers of fetal mice at gestation day 14. Fetal liver cell cultures were exposed to varying concentrations of benzene and additional cell cultures were exposed to various concentrations of a benzene metabolite mixture, composed of hydroquinone and benzoquinone. RNA was extracted from these cells and converted into complementary DNA. cDNA was then used in quantitative polymerase chain reactions to analyze a set of genes that are regulated by an antioxidant pathway. This pathway can be activated in response to oxidative stress, and a change in gene expression would indicate the presence of benzene or benzene metabolite toxicity in the liver at gestation day 14.

Author(s):  
Melford C. Egbujor ◽  
Samuel A. Egu ◽  
Vivian I. Okonkwo ◽  
Alifa D. Jacob ◽  
Pius I. Egwuatu ◽  
...  

The sustained interest in the design of potent antioxidants drugs over the years can be attributed to the indispensable roles antioxidants play in the mitigation of oxidative stress and its concomitant diseases. The high demand for exogenous antioxidants has been ascribed to the prevalence of oxidative stress-mediated diseases such as cancer, diabetes, stroke, cell aging, arteriosclerosis and central nervous system disorders occasioned by a biochemical disequilibrium between the production of free radicals and the body’s ability to eliminate these reactive species from the biological system. COVID-19 severity and death have been linked to a free radical generating process known as the cytokine storm. In an attempt to maintain optimal body function, antioxidant supplementation has increasingly become a wide spread practice because of antioxidants’ ability to directly scavenge free radicals, inhibit oxidative chain reactions thereby increasing the antioxidant defenses of the body. Recent data showed that researchers had made significant efforts to demonstrate the importance and timeliness of antioxidant therapy based on drug design from natural and synthetic sources. Therefore this review presents antioxidant drug design methodologies, identifying the lead and hits to provide a historical and up-to-date collection of research briefs on antioxidant drug design into a single piece in order to ensure easy accessibility, motivate readership and inspire future researches.


2021 ◽  
Vol 8 (1) ◽  
pp. 88
Author(s):  
Havizur Rahman ◽  
Putri Maya Sari ◽  
Fitrianingsih Fitrianingsih ◽  
Ai Kurniati ◽  
Fitri Kurniawati

Penelitian ini bertujuan untuk mengetahui aktifitas antioksidan dari ekstrak belut (Monopterus albus) yang hidup di perairan provinsi jambi. Radikal bebas cenderung menimbulkan reaksi berantai yang apabila terjadi di dalam tubuh akan dapat menimbulkan kerusakan sel yang berlanjut dan terus menerus terutama pada penyakit kronis seperti diabetes, hipertensi dan hiperkolesterol. Pencegahan dapat dilakukan dengan memberikan seyawa antioksidan, salah satunya asam amino. Di dalam al-Quran disebutkan bahwa bangkai yang halal untuk dimakan adalah ikan dan belalang. Belut merupakan salah satu jenis ikan yang memiliki kandungan albumin yang tinggi. Sampel daging belut yang telah difillet dan dipisahkan dari kepalanya, dipotong kecil-kecil dengan ukuran 1,5 cm2 dan dibalut dengan kain tipis dalam sebuah mangkuk, lalu dikukus, dipress, dan disentrifus.  diambil fase air dan minyak dan dibuang pengotornya dengan cara disaring, lalu dikeringkan menggunakan freeze drying sehingga diperoleh ekstrak belut dalam bentuk serbuk. Metode yang digunakan pada penelitian ini adalah Radical Scavenging method menggunakan senyawa kimia DPPH (2,2- difenil-1-pikrilhidrazil). Dari hasil penelitian ditemukan bahwa nilai IC50 ekstrak belut sebesar 29,0816 ppm. Ekstrak belut memiliki potensi menangkal radikal bebas dengan aktifitas kuat. Kata Kunci: Ektstrak Belut, Monopterus albus, Penangkal Radikal Bebas This study aims to determine the antioxidant activity of eel (Monopterus albus) extracts that live in the waters of the province of Jambi. Free radicals tend to cause chain reactions that occur in the body and will cause ongoing and continuous cell damage, especially in chronic diseases such as diabetes, hypertension and hypercholesterolemia. Prevention can be done by providing antioxidants, one of which is amino acids. In the Koran, it is stated that the carcasses that are lawful to eat are fish and grasshoppers. Eel is a type of fish that has a high albumin content. The eel meat sample that has been filled and given from its head, is cut into small pieces with a size of 1.5 cm2 and wrapped in a thin cloth in a container, then steamed, pressed, and centrifuged. the air and oil phases are taken and the impurities are removed by filtering, then they are dried using freeze drying in order to obtain the eel extract in powder form. The method used in this study is the Radical Scavenging Method using the chemical compound DPPH (2,2- diphenyl-1-pikrilhidrazil). From the research results it was found that the IC50 value of eel extract was 29.0816 ppm. Eel extract has the potential to ward off free radicals with strong activity.


Author(s):  
Vasyl Makolinets ◽  
Tamara Grashenkova ◽  
Volodymyr Moseichuk ◽  
Kyrylo Makolinets ◽  
Vladyslav Moseichuk

The paper presents an analysis of foreign scientific and medical data on the therapeutic factor — molecular hydrogen. The effectiveness of its application in the complex therapy of many diseases is revealed. The effect is achieved due to the small size of the mo­lecule, which passes through biological membranes and inhibits dangerous free radicals in the mitochondria, as well as in the nuc­leus, which reduces the possibility of DNA damaging. Molecular hydrogen neutralizes oxidants in the brain due to its ability to cross the blood-brain barrier. It normalizes the functions and metabolic processes in the body and, as an antioxidant, is selective: it does not affect the useful free radicals involved in important metabo­lic processes and selectively eliminates only the most dangerous oxidants — hydroxyl radicals. Interacting with them, hydrogen converts them into water molecules without the formation of by-products and chain reactions. Unlike other known antioxidants, molecular hydrogen does not disrupt normal metabolism, does not cause negative changes in cells, activates the body’s own anti­oxidant systems. The possibility and expediency of the use of molecular hydrogen in the case of pathology of the musculoskeletal system has been confirmed. The peculiarities of its effect on bone and cartilage tissue in the experiment are shown. It has been determined that the use of molecular hydrogen is a new pharmacological strategy aimed at the selective removal of ONOO—, and can be an effective method in the treatment of joint diseases. Because cartilage receives nutrients through a diffusion-loading mechanism, and molecular hydrogen penetrates rapidly into tissues, it can be useful for the prevention of diseases of joints of degenerative origin. It reduces oxidative stress and slows down the reduction of matrix proteins and inhibition of proteinase degradation. Its effectiveness has been proven after injuries to the spinal cord, muscles and tendons, comorbid diseases such as hypertension, coronary heart disease, diabetes and metabolic syndrome. Key words. Molecular hydrogen, hydrogen water, hydrogen inhalations, joint diseases, consequences of musculoskeletal injuries, comorbid pathology.


2020 ◽  
pp. 15-18
Author(s):  
Inna R. Kilmetova ◽  
◽  
Igor A. Rodin ◽  
Nazira I. Khayrullina ◽  
Nikolay G. Fenchenko ◽  
...  

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.


2019 ◽  
Vol 22 (7) ◽  
pp. 496-501
Author(s):  
Fatemeh Ahmadi-Motamayel ◽  
Parisa Falsafi ◽  
Hamidreza Abolsamadi ◽  
Mohammad T. Goodarzi ◽  
Jalal Poorolajal

Background: Cigarette smoke free radicals can cause cellular damage and different diseases. All the body fluids have antioxidants which protect against free radicals. Objective: The aim of this study was to evaluate salivary total antioxidant capacity and peroxidase, uric acid and malondialdehyde levels in smokers and a nonsmoking control group. Methods: Unstimulated saliva was collected from 510 males. A total of 259 subjects were current smokers and 251 were non-smokers. The levels of salivary total antioxidant capacity, uric acid, peroxidase and malondialdehyde were measured using standard procedures. Data were analyzed with t test and ANOVA. Results: The smokers were younger and dental hygiene index was higher than healthy nonsmoking controls. The mean total antioxidant capacity in smokers and nonsmokers was 0.13±0.07 and 0.21±011, respectively (P=0.001). Smokers had significantly lower peroxidase and uric acid levels than healthy controls. In addition, the mean malondialdehyde levels in the smokers and nonsmokers were 4.55 ±2.61 and 2.79 ±2.21, respectively (P=0.001). Conclusion: Cigarette smoke produces free radical and oxidative stress, causing many side effects. Salivary antioxidant levels decreased and malondialdehyde levels increased in smokers, indicating the high oxidative stress among smokers compared to nonsmokers. Cigarette smoke had deleterious effects on main salivary antioxidants levels.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1142
Author(s):  
Tsuyoshi Ando ◽  
Takeshi Nabeshima ◽  
Shingo Inoue ◽  
Mya Myat Ngwe Tun ◽  
Miho Obata ◽  
...  

In this study, we investigated severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) infection in cats in Nagasaki, Japan. In total, 44 of 133 (33.1%) cats with suspected SFTS were confirmed to be infected with SFTSV. Phylogenetic analyses of SFTSV isolates from cats indicated that the main genotype in Nagasaki was J1 and that unique reassortant strains with J2 (S segment) and unclassified genotypes (M and L segments) were also present. There were no significant differences in virus growth in cell cultures or fatality in SFTSV-infected mice between the SFTSV strains that were isolated from recovered and fatal cat cases. Remarkably, SFTSV RNAs were detected in the swabs from cats, indicating that the body fluids contain SFTSV. To evaluate the risk of SFTSV infection when providing animal care, we further examined the seroprevalence of SFTSV infection in veterinarian staff members; 3 of 71 (4.2%) were seropositive for SFTSV-specific antibodies. Our results provide useful information on the possibility of using cats as sentinel animals and raised concerns of the zoonotic risk of catching SFTSV from animals.


Author(s):  
Pozdnyakovа Т.А. ◽  
Kuleshovа Е.S. ◽  
Bubenchikov R.A.

The predominance of synthetic and genetically modified foods in the diet of a modern person often leads to disruption of natural metabolic processes and the accumulation of toxic free radicals in the body, which provokes the development of various diseases. Natural antioxidants from medicinal plants can help maintain health and stop the processes of peroxidation. In our opinion, Аstragalus onobrychis can become a promising source of natural antioxidants. The aim of this study was to establish the antioxidant activity in extracts from the herb Astragalus onobrychis. In order to obtain objective and reliable results during our research, we used two methods: the method of titrimetry and spectrophotometry of free radicals. The titrimetric method is based on the chemical interaction between an oxidizing agent (potassium permanganate) and natural antioxidants present in extracts from plant raw materials, since they exhibit the properties of reducing agents. The spectrophotometric method makes it possible to assess the value of antioxidant activity and the duration of the reaction by assessing the interaction of 2,2-diphenyl-1-picrylhydrazil with plant antioxidants. To establish the relationship between the antioxidant activity and the presence of phenolic compounds in the plant, the content of flavonoids and hydroxycinnamic acids in the herb Astragalus onobrychis was determined. As a result of the studies, the total antioxidant activity of extracts from the herb Astragalus onobrychis was established and it was revealed that its value depends on the type of extractant used, since this factor is associated with the content of various groups of natural antioxidants in the extraction. The data obtained indicate the prospects of using the herb Astragalus onobrychis as a source of natural antioxidants.


Author(s):  
Hanna Maria Elonheimo ◽  
Helle Raun Andersen ◽  
Andromachi Katsonouri ◽  
Hanna Tolonen

Alzheimer’s disease (AD) is the most common form of dementia, prevalent in approximately 50–70% of the dementia cases. AD affects memory, and it is a progressive disease interfering with cognitive abilities, behaviour and functioning of the person affected. In 2015, there were 47 million people affected by dementia worldwide, and the figure was estimated to increase to 75 million in 2030 and to 132 million by 2050. In the framework of European Human Biomonitoring Initiative (HBM4EU), 18 substances or substance groups were prioritized for investigation. For each of the priority substances, a scoping document was prepared. Based on these scoping documents and complementary review of the recent literature, a scoping review of HBM4EU-priority substances which might be associated with AD was conducted. A possible association between risk of AD and pesticides was detected. For mercury (Hg), association is possible but inconsistent. Regarding cadmium (Cd) and arsenic (As), the results are inconsistent but inclined towards possible associations between the substances and the risk of disease. The evidence regarding lead (Pb) was weaker than for the other substances; however, possible associations exist. Although there is evidence of adverse neurological effects of environmental substances, more research is needed. Environmental chemical exposure and the related hazards are essential concerns for public health, and they could be preventable.


2020 ◽  
Vol 22 (5) ◽  
pp. 987-992
Author(s):  
V. V. Zhelezko ◽  
I. A. Novikova

The article presents the data on assessment of functional features of neutrophils in 34 patients with systemic lupus erythematosus (SLE). Development of neutrophil extracellular traps (NETs) was evaluated in cell cultures incubated in vitro for 30 and 150 minutes (basal levels, NETBAS30 and NETBAS150, respectively), and in the presence of heat-inactivated S. аureus (strain ATCC 25923, 108 CFU/ml) (stimulated levels, NETST30 and NETST150, respectively). NET looks like thin free-lying extracellular fibrillar structures, 2-3 times exceeding the size of unchanged granulocyte. The result was expressed as percentage and relative amount of extracellular traps per 100 counted leukocytes. Phagocytic activity of neutrophils was evaluated as phagocytosis of S. аureus by counting the percentage of neutrophils that engulfed phagocytic index of microbial particles (PI); the average number of phagocytosed objects per neutrophil phagocytic number (PC). ROS-producing activity was determined in the reduction of Nitroblue Tetrazolium tested in spontaneous and stimulated S. аureus variants (NBTBAS and NBTST, respectively). The result was expressed as the percentage of formazan-positive cells per 100 white blood cells. Nitroxide-producing properties were determined using the Crow (1999) method in spontaneous and stimulated samples for the accumulation of the nitrated amino acid tyrosine (3-nitrothyrosine, 3-NTBAS, and 3-NTST, respectively). We revealed a decrease in ROS production, phagocytosis and NO-forming activity of neutrophils associated with increased netosis. Activation of the netosis was observed in cell cultures without stimulation, indicating the in vivo formation of networks in SLE. The NET increase is most pronounced in the patients with lupus nephritis (p < 0.05), and in remission of the disease (p < 0.05). We have revealed a correlation of NET formation parameters with duration and degree of SLE activity (rs = -0.6; p = 0.001, and rs = 0.39; p = 0.02, respectively); autoantibody titers (anti-dsDNA and ANA) (rs = 0.67; р = 0.047 and rs = 0.59; р = 0.034, respectively); prothrombin complex activity (rs = 0.6; p = 0.036), as well and urea and creatinine levels (rs = 0.47; p = 0.037 and rs = 0.39; p = 0.048, respectively). The parameters of NETs can be considered a promising biomarker for verifying the diagnosis of SLE, evaluation of clinical activity, disease severity, and predicting the development of complications.


2011 ◽  
Vol 65 (3-4) ◽  
pp. 247-256
Author(s):  
Jelka Stevanovic ◽  
Suncica Borozan ◽  
Slavoljub Jovic ◽  
Igor Ignjatovic

Free radicals occur constantly during metabolism and take part in numerous physiological processes, such as: intra-cellular and inter-cellular signalization, gene expression, removal of damaged or senescent cells, and control of the tone of blood vessels. However, there is an increased quantity of free radicals in situations of so-called oxidative stress, when they cause serious damage to cellular membranes (peroxidation of their lipids, damage of membrane proteins, and similar), to interior cellular protein molecules, as well as DNA molecules and carbohydrates. This is precisely why the organism has developed numerous mechanisms for removing free radicals and/or preventing their production. Some of these are enzyme-related and include superoxide-dismutase, catalase, glutathione-peroxidase, and others. Other, non-enzyme mechanisms, imply antioxidative activities of vitamins E and C, provitamin A, coenzyme Q, reduced glutation, and others. Since free radicals can leave the cell that has produced them and become dispersed throughout the body, in addition to antioxidative defense that functions within cellular structures, antioxidant extra-cellular defense has also been developed. This is comprised by: transferrin, lactoferrin, haptoglobin, hemopexin, ceruloplasmin, albumins, extra-cellular isoform SOD, extracellular glutathione-peroxidase, glucose, bilirubin, urates, and many other molecules.


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